Studies of the morphological effects of antimalarial drugs on malarial parasites yield important information on the site of action of the drugs. Changes in the structure of the malarial parasites furnish clues to the mode of drug action. In the current year, we undertook clinical and morphological studies on the mode of action of clindamycin and its N-demethyl - 4' - pentyl analogue against P. knowlesi in rhesus monkeys. By light microscopy, the first indication of drug effect on the parasite was seen after 24 hours. By 48-60 hours dissociation of the cytoplasm from the nucleus and general disruption and vacuolation of the cytoplasm were noted. The ultrastructural changes induced by clindamycin were observed in all stages. Most noticeable changes occurred in ribosomes. The affected ribosomes showed an electron-lucent zone in the center. These morphological changes were also seen in isolated ribosomes of P. knowlesi treated with clindamycin. Negatively stained, isolated ribosomes of P. knowlesi showed that about 60 percent of them possess and electron-opaque zone while only 10 percent of controlled ribosomes showed such a change. This result suggests that clindamycin primarily acts on ribosomes of malarial parasites. This study will be continued by electron microscope autoradiography on the parasites treated with H3- clindamycin.